The formulation and presentation of medicaments

ABSTRACT

A medicament package ( 10,30 ) comprises a vessel ( 12,32 ) adapted to hold a quantity of a liquid vehicle. The vessel ( 12,32 ) has an opening formed therein, to which opening is bonded a deformable enclosure ( 18,38 ). A medicament container ( 20 ) that contains a unit dose of a medicament is received within the enclosure ( 18,38 ), such that by deformation of the enclosure ( 18,38 ) the container ( 20 ) may be dislodged from the enclosure ( 18,38 ) into the vessel ( 12,32 ), whereby the medicament may escape from the container ( 20 ) and mix with the liquid vehicle. The medicament contained within the medicament container ( 20 ) is most preferably in admixture with sodium chloride.

This invention relates to improvements in the formulation andpresentation of medicaments, and in particular to the formulation andpackaging of medicaments that are administered in solution orsuspension.

Many medicaments are necessarily or preferably administered in solutionor suspension. Such solutions or suspensions may be administered usingbottles, syringes, spray pumps or by any other suitable method. Forconvenience, such medicaments are generally packaged and sold aspre-prepared solutions or suspensions, many of which comprise sodiumchloride in order to render them isotonic with body fluids.

However, certain medicaments are unstable when formulated as a solutionor suspension. Such medicaments may degrade over time, with a loss ofactivity or even the generation of products that are not merelyinactive, but harmful. In such cases, it is therefore necessary that thesolution or suspension must be used within a short time of having beenmade up. The medicament may therefore be formulated in dry form, eg as apowder, and added to a measured volume of solvent by the patientimmediately prior to administration. The medicament may, for instance,be packaged in a capsule or other container that is cut or ruptured andthe medicament then added to the solvent and stirred, thereby formingthe solution or suspension to be administered. Various delivery systemshave also been proposed for such medicaments, in which the medicament,in dry form (eg a powder), is held separate from the solvent until it isdesired to make up the solution or suspension (ie until just beforeuse). Some form of barrier or membrane between the powder and thesolvent is then broken, allowing the powder and the solvent to becomemixed.

Disadvantages of medicament packaging of the type described aboveinclude the possibility of debris being produced when the capsule orcontainer is cut or ruptured, or the membrane or barrier is broken,which may contaminate the medicament solution or suspension. Inaddition, the process of cutting or rupturing the capsule or container,adding the medicament to the solvent and then stirring is time consumingand may require considerable dexterity, particularly where the quantityof medicament is very small.

Furthermore, the process of filling the container with the desired doseof powdered medicament generally requires the use of a diluent, which isoften present in an amount that considerably exceeds that of the activeingredient itself. Again, this is particularly the case where thequantity of medicament is very low, as for very potent medicaments.Diluents that are used are essentially inert materials such as lactose.Whilst such materials are normally not harmful, they do representconstituents of the pharmaceutical formulation that are of no benefit tothe patient, and as such it would generally be desirable to omit them.

There have now been devised improvements in the formulation andpresentation of medicaments that overcome or substantially mitigate theabove-mentioned and/or other disadvantages associated with the priorart.

According to the invention, there is provided a medicament packagecomprising a vessel adapted to hold a quantity of a liquid vehicle, thevessel having an opening formed therein, to which opening is bonded adeformable enclosure, within which enclosure there is received amedicament container that contains a unit dose of a medicament, suchthat by deformation of the enclosure the container may be dislodged fromthe enclosure into the vessel, whereby the medicament may escape fromthe container and mix with the liquid vehicle.

The medicament package according to the invention is advantageousprimarily in that the medicament can be stored within the package inisolation until the user wishes to prepare a solution or suspension foradministration. The action of dispensing the medicament into the liquidvehicle is also very straightforward, requiring only finger pressure tobe applied to the deformable enclosure, thereby allowing patients withlimited dexterity to prepare the solution or suspension. The release ofthe medicament container from the enclosure does not involve thebreaking or rupturing of the container or any membrane or barrier, andtherefore does not lead to the generation of any debris that could beharmful to the patient (eg if inhaled). Furthermore, the containeritself, when released from the enclosure into the vessel, may functionas an agitator that promotes efficient mixing of the medicament and theliquid vehicle.

The medicament may escape from the medicament container by virtue of thelatter being formed with one or more dispensing apertures, through whichthe medicament may exit the container and/or liquid can enter thecontainer and flush out the contents of the container. Alternatively,the medicament container may be formed as two or more components, theintegrity of the container being maintained by its engagement by theenclosure, and that integrity being lost once the container is releasedfrom the enclosure.

The vessel may take any suitable form. The vessel may, for instance,have the general form of a cup, a bottle or flask, or a syringe. Thevessel may, where appropriate, be a part of a suitable delivery device,eg a nebuliser or a syringe.

The enclosure may be bonded to the body of the vessel, or may form partof a separate component, eg a cap or other closure, that engages thevessel, eg by a threaded connection.

The medicament package may be supplied with a suitable volume of liquidvehicle present in the vessel. Alternatively, the vessel may be chargedwith a suitable volume of liquid vehicle by the user immediately priorto use.

Following mixing of the medicament with the liquid vehicle containedwithin the vessel, the solution or suspension of medicament may beadministered directly from the vessel. Alternatively, the solution orsuspension may be transferred from the vessel to another container foradministration. For example, the solution or suspension may be pouredinto a nebuliser or drawn up into a syringe.

In some embodiments, the enclosure is formed with one or more apertures,most commonly a single central aperture, that is closed, while themedicament container is held within the enclosure, by the medicamentcontainer. When the medicament container has been dislodged from theenclosure, that aperture then functions as an outlet by which thesolution or suspension may be dispensed from the vessel. For example,the solution or suspension may be drawn up into a syringe via a needleor cannula inserted through the aperture, or expelled through theaperture by squeezing of the vessel (where the vessel, or a suitablepart of the vessel) is of a flexible material). Where the aperture isrelatively small, and the surface tension of the solution or suspensionso permits, the solution or suspension may be dispensed from the vesselthrough the aperture drop-wise, simply by inverting the vessel and ifnecessary applying gentle squeezing and/or shaking. In a furtherembodiment of the invention, there is provided a second deformableelement, which may be similar in form to the deformable enclosure (butwhich does not have an aperture). Depression of the second deformableelement provides a pumping action by which the solution or suspensioncan be dispensed via the aperture in the first enclosure.

The deformable enclosure is preferably bonded to the periphery of theopening and extends therefrom such that the enclosure has the form of acup and the opening constitutes an open mouth of the enclosure. Ingeneral, the shape of the cup will conform to that of the medicamentcontainer. Most preferably the enclosure fits closely around at leastthat part of the container which is formed with the dispensingaperture(s). The material of the enclosure may extend beyond the openingto which it is bonded, preferably with an inwardly extending lip toenhance the retention of the medicament container within the enclosure.

The arrangement is most preferably such that the medicament container isreceived by the enclosure with a close fit, and pressure applied, inuse, by a user to the exterior of the enclosure deforms the enclosureand causes the container to be dispensed from the enclosure, through theopen mouth thereof, and into the vessel.

The deformable enclosure may be bonded directly to the body of thevessel, or to the cap or other closure. Alternatively, the enclosure maybe bonded to a rigid intermediate component in which the opening isformed, that is in turn connected to the body of the vessel (or capetc), eg by means of an interference fit. The intermediate component maytake the form of a support ring, with the deformable enclosure bonded tothe interior of the support ring.

The intermediate component is preferably made of plastics material, andmost preferably polypropylene. The deformable enclosure is preferably ofelastomeric material. The elastomeric material is preferably waterresistant and non-toxic. A particularly suitable elastomeric material isa medical grade thermoplastic rubber, eg that referred to as SANTOPRENE(Advanced Elastomer Systems NV/SA, Leicester, United Kingdom).

The vessel, or at least the part of the vessel to which the enclosure isbonded, and the enclosure may be injection moulded in a two-stepprocess. In such a process, the relevant part of the vessel ispreferably injection moulded in a first step. The enclosure is theninjection moulded onto the first moulding. The materials used for therelevant part of the vessel and the enclosure are preferably chosen suchthat they adhere when the second material is moulded onto the first. Thepreferred materials polypropylene and SANTOPRENE adhere in that fashion.

The medicament container preferably comprises two (or more) cooperatingcomponents, most preferably a cup and a closure which fit together. Thecooperating components may fit together with a close, interference fit.In such a case, the enclosure will generally maintain its integrity whendislodged from the enclosure and is therefore provided with at least oneopening through which the contents of the container can escape.Alternatively, the cooperating components may engage only loosely, beingheld together by virtue of being held in the enclosure, and may separateonce released from the enclosure, thereby allowing the contents toescape. The container is preferably generally cylindrical, eg in theform of a drum. The medicament container is preferably made of plasticsmaterial of low moisture permeability and is most preferably made ofhigh density polyethylene. The components of the medicament containerare preferably injection moulded.

The entire medicament package according to the invention may be renderedsterile, eg by gamma-irradiation. Many embodiments of the invention willbe completely closed systems, and in such embodiments release of themedicament container from the enclosure, and the consequent generationof the required solution or suspension, will occur without any loss ofsterility.

Most preferably, the medicament container contains a unit dose of apharmaceutical formulation comprising the unit dose of medicament inadmixture with sodium chloride.

In another aspect, the invention provides a pharmaceutical formulationcomprising a solid medicament intended for dissolution or dispersion ina liquid vehicle, the medicament being in admixture with sodiumchloride. The formulation according to the invention is most preferablycontained within the medicament container of the medicament packagedescribed above.

The formulation according to the invention is advantageous primarily inthat it does not contain any excipient intended solely to act as acarrier to aid the handling and dosing of the active medicament.Instead, it is the sodium chloride, which is present in order to adjustthe tonicity of the solution or suspension formed by dissolution ordispersion of the medicament, that also performs the function of apowder diluent.

The medicament and the sodium chloride are both present in theformulation in solid form. For example, both components may be presentin particulate form, the formulation being prepared by simple admixtureof particles of both materials. Alternatively, the formulation maycomprise a solid body made up of both materials. Such a solid body maybe prepared by compaction of a powder mixture of medicament and sodiumchloride.

The proportions of medicament and sodium chloride in the formulationaccording to the invention may vary widely, but in general the sodiumchloride will be present as the major constituent. In general, theformulation will comprise less than 50%, and more preferably less than40%, less than 30%, less than 20%, or less than 10% w/w of medicament.In general, the formulation will comprise more than 50%, and morepreferably more than 60%, more than 70%, more than 80% or more than 90%w/w of sodium chloride.

The formulation may further comprise one or more other excipients. Wherepresent, such excipients will be present in relatively low amounts (egless than 10%, more preferably less than 5% w/w in total). However, suchother excipients will more commonly be formulated as part of the liquidvehicle with which the formulation is mixed prior to administration.

Most commonly, the required unit dose of medicament will be formulatedwith sufficient sodium chloride to yield an isotonic solution orsuspension when the formulation is mixed with a given volume of liquid(normally water). The unit dose of medicament may be very low, eg of theorder of micrograms. To achieve isotonicity, a concentration of sodiumchloride of 0.9% w/v is required.

Thus, to achieve an isotonic solution with a volume of 5 cm³, therequired dose of medicament is formulated with 45 mg of sodium chloride.If the volume is to be 3 cm³, then the quantity of sodium chloriderequired is 27 mg.

Bulk quantities of the formulation according to the invention may beprepared using essentially conventional techniques that will be familiarto those skilled in the art. Likewise, unit doses of the formulation maybe filled into suitable containers by known techniques, similar totechniques that are conventionally used for the filling of powdermixtures (eg mixtures of medicament and lactose) into capsules or thelike.

The unit dose of the formulation, filled into a suitable container, mayif necessary or desired be rendered sterile, eg by gamma-irradiation.The unit dose of the formulation may be supplied with a vesselcontaining the required quantity of liquid vehicle, which may furthercomprise other excipients (eg surfactant, etc). Alternatively, thepatient may himself measure the required quantity of liquid and add theunit dose of powder to it, immediately prior to use.

According to another aspect of the invention, there is provided the useof sodium chloride as a diluent for a medicament in solid form that isintended for dissolution or dispersion in a liquid vehicle prior toadministration.

The invention further provides a process for the preparation of apharmaceutical formulation, which process comprises admixing amedicament in solid form with particulate sodium chloride.

It will be understood that all references to a medicament as used hereinencompass the use of two or more different medicaments in admixture.

Examples of medicaments that may be formulated in accordance with theinvention include drugs intended for administration by inhalation. Suchdrugs include

a) bronchodilators (β₂-agonists), eg fenoterol, formoterol, salmeteroland salbutamol;

b) steroids, eg budesonide, fluticasone and triamcinolone acetonide;

c) anticholinergic agents, eg ipratropium bromide and oxitropiumbromide;

d) antiallergic agents, eg sodium cromoglycate and nedocromil sodium;

e) antibiotics, eg tobramycin;

f) proteins and peptides, eg insulin;

g) mucolytics; and

h) vaccines.

Mixtures of medicaments that may be used include mixtures of:

a) bronchodilators (β₂-agonists) and steroids, eg

formoterol and budesonide,

salmeterol and fluticasone,

formoterol and fluticasone,

salmeterol and budesonide;

b) anticholinergics and steroids, eg

ipratropium bromide and budesonide,

ipratropium bromide and fluticasone,

oxitropium bromide and budesonide,

oxitropium bromide and fluticasone; and

c) antiallergic agents and steroids or anti-cholinergics, eg

sodium cromoglycate and budesonide,

sodium cromoglycate and fluticasone,

sodium cromoglycate and ipratropium bromide,

sodium cromoglycate and oxitropium bromide,

nedocromil sodium and budesonide,

nedocromil sodium and fluticasone,

nedocromil sodium and ipratropium bromide;

nedocromil sodium and oxitropium bromide.

The invention will now be described in greater detail, by way ofillustration only, with reference to the accompanying drawings, in which

FIG. 1 is a side view of a first embodiment of a medicament packageaccording to the invention;

FIG. 2 is a diametrical section of the medicament package of FIG. 1;

FIG. 3 is diametrical section of a medicament container which forms partof the medicament package according to the invention;

FIG. 4 is a perspective view of the medicament container of FIG. 4;

FIG. 5 is a diametrical section of a second embodiment of a medicamentpackage according to the invention; and

FIG. 6 is a side view of a support ring and deformable enclosure whichform part of the medicament package of FIG. 5.

A first embodiment of a medicament package according to the invention isshown in FIGS. 1 and 2 and is generally designated 10. The medicamentpackage 10 comprises a vessel 12 and a cap 14. The vessel 12 is formedin a rigid plastics material and the cap 14 is formed in polypropylene.

The vessel 12 is generally cylindrical with a closed lower end and anopen upper end (as viewed in FIGS. 1 and 2). The diameter of the vessel12 gradually increases from the lower to the upper end. The lowersurface of the vessel 12 is flat so that the medicament package 10 mayrest on a substantially flat surface in an upright position.

The upper end of the vessel 12 is formed with an external thread forengagement with the cap 14, which in turn is formed with aninternally-threaded downwardly-depending circumferential skirt. Theexternal surface of the cap 14 is formed with vertical ribs, whichconstitute a grip 15 that facilitates application and removal of the cap14 from the vessel 12. The cap 14 has a circular aperture at its centre,to the periphery of which is bonded a deformable enclosure 18.

The deformable enclosure 18 is generally cylindrical, with a dome-shapedupper part. The open lower end of the enclosure 18 is formed with aninwardly extending lip 19. The deformable enclosure 18 holds amedicament container 20 (shown in more detail in FIGS. 3 and 4) whichfits closely within the enclosure 18 with the lip 19 lying alongside thelower surface of the container 20.

The deformable enclosure 18 is formed in an elastomeric material. Asuitable elastomeric material is medical grade Santoprene thermoplasticrubber from Advanced Elastomer Systems.

The medicament container 20 is shown in more detail in FIGS. 3 and 4.The medicament container 20 comprises an inverted cup 22 and a closure24, both of plastics material. The cup 22 conforms in shape to theinterior of the enclosure 18, comprising a cylindrical main body and aclosed upper end that is of generally domed shape.

The cylindrical main body of the cup 22 is formed with a series ofequiangularly spaced rectangular openings 26 which extend upwardly fromthe open end of the cup 22 along the majority of the height of the mainbody.

The closure 24 comprises a disc with a diameter identical to theexternal diameter of the cup 22 and an upstanding rim that is receivedclosely within the lower end of the cup 22 with an interference fit. Therim extends upwardly to occlude the lower part of each opening 26 in thecup 22, as shown in FIG. 4. The container 20 is dimensioned so that thecontainer 20 is closely received with an interference fit within theenclosure 18 and the lip 19 lies alongside the lower surface of thecontainer 20.

The vessel 12, cap 14 and deformable enclosure 18 are formed byinjection-moulding. The cap 14 and deformable enclosure 18 are formed ina two-shot injection moulding process in which elastomeric material,which forms the deformable enclosure 18, is injection-moulded onto apreviously injection-moulded cap 14, thereby bonding the deformableenclosure 18 to the cap 14.

The medicament package is assembled by filling a unit dose of medicamentinto the cup 22 (normally with the latter in an inverted condition), andthen applying the closure 24 to the open mouth of the cup 22. Theassembled medicament container 20 is then pressed into the enclosure 18.Alternatively, the cup 22 may be inserted into the enclosure 18, the cup22 then filled with the dose of medicament and the closure 24 thenapplied to the open mouth of the cup 22. The latter approach may also beused for embodiments of the invention in which the components of thecontainer are not fixed together, but which separate after release fromthe enclosure, rather than having dispensing apertures 26. Finally, thecap 14 is threadedly engaged with the vessel 12. The vessel may befilled with a quantity of liquid (most commonly water, or an aqueoussolution) before the cap 14 is fitted. Alternatively, the package may besupplied without any liquid present in the vessel, the cap 14 beingremoved and liquid introduced by the user prior to use of the package.

In use, medicament is contained within the medicament container 20 andthe apertures 26 of the container 20 are sealed by the deformableenclosure 18, thereby preventing escape of the medicament from thecontainer 20. The vessel 12 is either pre-charged with the liquidvehicle or liquid is introduced into the vessel 12, immediately prior toadministration, by temporarily disengaging the cap 14 from the enclosure18. The liquid contained within the enclosure 18 is prevented fromcoming into contact with the medicament by the close fit between thedeformable enclosure 18 and the container 20.

In order to prepare the solution or suspension for administration, themedicament is introduced into the liquid contained within the vessel 12by applying downward finger pressure on the deformable enclosure 18,thereby causing the container 20 to be displaced from the enclosure 18and to fall into the liquid. When the container 20 is released from theenclosure 18 the openings 26 are exposed, and consequently themedicament can escape from the container 20 via the openings 26. Theliquid may also flow into the container 20 and flush the medicament outof the container 20. The process of dispersion and/or dissolution of themedicament in the liquid may be facilitated by shaking of the vessel 12,in which case the container 20 may itself act as a mechanical agitator.

After mixing of the medicament and liquid, the prepared solution orsuspension may then be dispensed from the medicament package 10 byremoving the cap 14 and pouring the solution or suspension into asuitable administration device, eg a nebuliser. It will be appreciatedthat in other embodiments the vessel may actually form part of such adevice (or may be fitted into such a device) and will be provided withmeans enabling the direct administration of the solution or suspensionfrom the vessel.

Turning now to FIGS. 5 and 6, a second embodiment of a medicamentpackage according to the invention is shown and generally designated 30.The second embodiment 30 is similar to the first embodiment 10, in thatit comprises a vessel 32, a cap 34 and a deformable enclosure 38.However, the deformable enclosure 38 is bonded, not directly to the cap34, but to a support ring 36 to form a dosing assembly (generallydesignated 39) that may be separated from the cap 34, as shown in FIG.5. As with the first embodiment 10, a medicament container 20 is closelyreceived, with an interference fit, within the deformable enclosure 38.

The deformable enclosure 38 and support ring 36 are formed by a two-shotinjection moulding process as described above in respect of thedeformable enclosure 18 and cap 14 of the first embodiment 10.

The support ring 36 is of L-shaped cross-section, comprising acylindrical ring with an outwardly extending flange, as shown moreclearly in FIG. 6. The external surface of the ring fits closely, withan interference fit, within a corresponding circular aperture 37 in thecentre of the upper surface of the cap 34.

In use, liquid is introduced into the vessel 32. This may be done byremoving the cap 34 from the vessel 32, or alternatively via thecircular aperture 37 with the dosing assembly 39 removed. In the lattercase, a dosing assembly 39 is then positioned, with an interference fit,within the aperture 37 of the cap 14. Otherwise, the cap 34, with thedosing assembly 39 in place, is engaged with the vessel 32. As with thefirst embodiment 10, the liquid contained within the vessel 32 isprevented from coming into contact with the medicament by the close fitbetween the deformable enclosure 38 and the container 20.

As for the first embodiment, in order to prepare the solution orsuspension, the medicament is introduced into the liquid by applyingdownward pressure on the deformable enclosure 18, thereby causing thecontainer 20 to fall into the liquid.

After use, the dosing assembly 39 may be removed from the aperture 37 ofthe cap 34, and replaced by another. The medicament package 30 may thenbe re-used, as described above, with a dosing assembly 39 containing anew medicament container 20.

The following Examples illustrate unit doses of medicament that may becontained within the medicament container 20.

EXAMPLE 1

Sodium cromoglycate 20 mg Sodium chloride 45 mg

The unit dose having the above composition is intended for dissolutionin 5 ml of water, resulting in an isotonic solution of sodiumcromoglycate.

EXAMPLE 2

Salbutamol 100 μg Sodium chloride 18 mg

The unit dose having the above composition is intended for dissolutionin 2 ml of water, resulting in an isotonic solution of salbutamol.

EXAMPLE 3

Budesonide 200 μg Formoterol 4.5 μg Sodium Chloride 27 mg

The unit dose having the above composition is intended for dissolutionin 3 ml of water, resulting in an isotonic solution of the two activeingredients.

32. A medicament package comprising a vessel adapted to hold a quantityof a liquid vehicle, the vessel having an opening formed therein, towhich opening is engaged a deformable enclosure, within which enclosurethere is received a medicament container that contains a unit dose of amedicament, wherein the entire medicament package has been renderedsterile and is arranged such that by deformation of the enclosure thecontainer may be dislodged from the enclosure into the vessel, wherebythe medicament may escape from the container and mix with the liquidvehicle.
 33. A medicament package as claimed in claim 32, wherein themedicament container is formed with one or more dispensing apertures,through which, in use, the medicament may exit the container and/orliquid can enter the container.
 34. A medicament package as claimed inclaim 32, wherein the medicament container is formed as two or morecomponents, the integrity of the container being maintained by itsengagement by the enclosure, and that integrity being lost once thecontainer is released from the enclosure.
 35. A medicament package asclaimed in claim 32, wherein the enclosure is formed with an aperturethat is closed, while the medicament container is held within theenclosure, by the medicament container such that when the medicamentcontainer has been dislodged from the enclosure, the aperture thenfunctions as an outlet by which the formed solution or suspension may bedispensed from the vessel.
 36. A medicament package as claimed claim 32,wherein the deformable enclosure is bonded to the periphery of theopening and extends therefrom such that the enclosure has the form of acup and the opening constitutes an open mouth of the enclosure.
 37. Amedicament package as claimed in claim 36, wherein the enclosure fitsclosely around at least that part of the container which is formed withthe dispensing aperture(s).
 38. A medicament package as claimed in claim37, wherein the arrangement is such that the medicament container isreceived by the enclosure with a close fit, and pressure applied, inuse, by a user to the exterior of the enclosure deforms the enclosureand causes the container to be dispensed from the enclosure, through theopen mouth thereof, and into the vessel.
 39. A medicament package asclaimed claim 32, wherein the enclosure is bonded to the body of thevessel.
 40. A medicament package as claimed in claim 32, wherein theenclosure forms part of a separate component that engages the vessel.41. A medicament package as claimed in claim 40, wherein the deformableenclosure is bonded to a rigid intermediate component in which theopening is formed, that is in turn connected to the body of the vessel,and the intermediate component takes the form of a support ring, withthe deformable enclosure bonded to the interior of the support ring. 42.A medicament package as claimed in claim 32, wherein the deformableenclosure is of elastomeric material.
 43. A medicament package asclaimed in claim 32, wherein the vessel, or at least the part of thevessel to which the enclosure is bonded, and the enclosure is injectionmoulded in a two-step process in which the relevant part of the vesselis injection moulded in a first step, and the enclosure is theninjection moulded onto the first moulding.
 44. A medicament package asclaimed in claim 32, wherein the medicament container contains a unitdose of a pharmaceutical formulation comprising the unit dose ofmedicament in admixture with sodium chloride.
 45. A medicament packageas claimed in claim 44, wherein the medicament and the sodium chlorideare both present in the formulation in particulate form.
 46. Amedicament package as claimed in claim 44, wherein the formulationcomprises a solid body made up of the medicament and sodium chloride.47. A medicament package as claimed in claim 46, wherein the solid bodyis prepared by compaction of a powder mixture of medicament and sodiumchloride.
 48. A medicament package as claimed in claim 44, wherein theformulation comprises less than 50% w/w of medicament.
 49. A medicamentpackage as claimed in claim 44, wherein the formulation comprises morethan 50% w/w of sodium chloride.
 50. A medicament package as claimed inclaim 44, wherein the unit dose of medicament is formulated withsufficient sodium chloride to yield an isotonic solution or suspensionwhen the formulation is mixed with a given volume of liquid.
 51. Apharmaceutical formulation comprising a solid medicament intended fordissolution or dispersion in a liquid vehicle, the medicament being inadmixture with solid sodium chloride.
 52. A pharmaceutical formulationas claimed in claim 51, wherein the medicament and the sodium chlorideare both present in the formulation in particulate form.
 53. Apharmaceutical formulation as claimed in claim 51, wherein theformulation comprises a solid body made up of the medicament and sodiumchloride.
 54. A pharmaceutical formulation as claimed in claim 53,wherein the solid body is prepared by compaction of a powder mixture ofmedicament and sodium chloride.
 55. A pharmaceutical formulation asclaimed in claim 51, wherein the formulation comprises less than 50% w/wof medicament.
 56. A pharmaceutical formulation as claimed in claim 51,wherein the formulation comprises more than 50% w/w of sodium chloride.57. A pharmaceutical formulation as claimed in claim 51, wherein theunit dose of medicament is formulated with sufficient sodium chloride toyield an isotonic solution or suspension when the formulation is mixedwith a given volume of liquid.
 58. A pharmaceutical formulation asclaimed in claim 51, wherein the medicament is selected from the groupconsisting of bronchodilators (β₂-agonists), steroids, anticholinergicagents, antiallergic agents, antibiotics, proteins and peptides,mucolytics, and vaccines.
 59. The use of solid sodium chloride as adiluent for a medicament in solid form that is intended for dissolutionor dispersion in a liquid vehicle prior to administration.
 60. A processfor the preparation of a pharmaceutical formulation, which processcomprises admixing a medicament in solid form with particulate sodiumchloride.